Highly solvatochromic and tunable fluorophores based on a 4,5-quinolimide scaffold: Novel CDK5 probes

Novel 4,5-quinolimide-based fluorophores are more solvatochromic and red-shifted than known naphthalimide analogues. Conjugation of one of these fluorophores to a peptide derived from CDK5 kinase demonstrated its sensitivity for monitoring the interaction with its regulatory partner p25. Introduction of the quinolimide-labelled peptide into living glioblastoma cells probed the interaction with endogenous p25.The work was supported by the Spanish Ministerio de Economía y Competividad grant SAF2012-32209 and the CSIC grant 2012280E096. J. A. G.-V. held a JAEdoc research contract from the CSIC and now is supported by a Marie-Curie fellowship EC-FP7 Framework (PIEF-GA-2013-623151). The work was also supported by the CNRS and a grant from Canceropole GSO 2015-E03 to MCM and has benefited from the facilities and expertise of the Montpellier RIO imaging facility (www.mri.cnrs.fr) at the Centre de Recherches en Biochimie Macromoléculaire, MontpellierPeer Reviewe

Error 404: Organization not found. Intergroup unión disputes in the argentinian it sector (2015-2020)

El siguiente artículo propone abordar las disputas por representación sindical dentro del sector informático Argentino. A pesar de haber habido un crecimiento en la actividad sindical en los lugares de trabajo, predomina un modelo no sindicalizado de relaciones laborales. Con el cambio de gobierno en 2015 se renuevan las oportunidades políticas para todos los actores y las empresas aprovecharan el contexto para disciplinar a la fuerza de trabajo. Por otro lado el gremio con mayor representación, la Unión Informática no logra redefinir sus objetivos estratégicos y resurgen los conflictos laborales con cuestionamientos al interior de la organización. Sindicatos que se encontraban inactivos o desinteresados por representar a los informáticos entraran en escena para disputar la personería gremial o encuadrar a los trabajadores bajo su convenio colectivo.The following article proposes to define disputes over union representation within the Argentine IT sector. Despite the groth in union activity, a nonunion model of labor relations predominates. With the change of government in 2015, political opportunities are renewed for all actors and companies will take advantage of the context to discipline the workforce. On the other hand, the union with the largest representation, the Unión Informática, fails to redefine its strategic choices and labor conflicts resurface with questions within the organization. Unions that were inactive or uninterested in representing these employees, entered the scene to dispute the status of the union or frame the workers under their collective agreement.Fil: del Fueyo, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones "Gino Germani"; Argentin

Los desafíos organizativos de los trabajadores de la Industria 4.0: reflexiones a partir de la experiencia sindical de los informáticos en Argentina

En esta exposición buscamos problematizar sobre las dificultades y desafíos organizativos de los trabajadores Informáticos a partir de la lectura de sus experiencias colectivas e institucionales, el legado histórico del movimiento obrero plasmado en los sindicatos con mayor trayectoria y en la legislación laboral, y en las nuevas formas de trabajo y otras formas de organización por fuera del sindicalismo tradicional. Para ello tendremos en cuenta los repertorios de protesta escogidos por las distintas organización que buscan representar a este universo de trabajadores, el tipo de alianzas que entablan con otros actores, su accionar frente a las oportunidades políticas, y las innovaciones que introducen para afrontar los obstáculos no previstos por el marco institucional.Facultad de Humanidades y Ciencias de la Educació

Oncolytic Adenoviruses and Immunopeptidomics: A Convenient Marriage

Oncolytic viruses (OVs) are biological therapeutic agents that selectively destroy cancer cells while sparing normal healthy cells. Besides direct oncolysis, OV infection induces a proinflammatory shift in the tumor microenvironment and the release of tumor-associated antigens (TAAs) that might induce an anti-tumor immunity. Due to their immunostimulatory effect, OVs have been explored for cancer vaccination against specific TAAs. However, this approach usually requires genetic modification of the virus and the production of a new viral vector for each target, which is difficult to implement for low prevalent antigens. In a recent study, Chiaro et al. presented an elegant proof of concept on how to implement the PeptiCRAd vaccination platform to overcome this limitation for the treatment of mesothelioma. Authors showed the feasibility of identifying immunogenic TAAs in human mesothelioma and using them to coat oncolytic adenovirus particles. The result was a customized virus-based cancer vaccine that circumvents time and resource-consuming steps incurred from genetically engineering viruses. Although some questions remain to be addressed, this interesting approach suggests novel strategies for personalized cancer medicine using oncolytic virotherapy

Small-molecule TIP60 inhibitors enhance regulatory T cell induction through TIP60-P300 acetylation crosstalk

Foxp3 acetylation is essential to regulatory T (Treg) cell stability and function, but pharmacologically increasing it remains an unmet challenge. Here, we report that small-molecule compounds that inhibit TIP60, an acetyltransferase known to acetylate Foxp3, unexpectedly increase Foxp3 acetylation and Treg induction. Utilizing a dual experimental/computational approach combined with a newly developed FRET-based methodology compatible with flow cytometry to measure Foxp3 acetylation, we unraveled the mechanism of action of these small-molecule compounds in murine and human Treg induction cell cultures. We demonstrate that at low-mid concentrations they activate TIP60 to acetylate P300, a different acetyltransferase, which in turn increases Foxp3 acetylation, thereby enhancing Treg cell induction. These results reveal a potential therapeutic target relevant to autoimmunity and transplant.NIH AI141710Grant PID2020-114256RB-I00 funded by MCIN/AEI/10.13039/501100011033Grants P21_00212 and A-FQM-386-UGR20 funded by FEDER/Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y Universidade

Smart lanthanide antennas for sensing water

Two new families of lanthanide antennas are described. 8-Methoxy- 4,5-dihydrocyclopenta[de]quinolin-2(1H)-one phosphonates or carboxylates behave as selective antennas exhibiting Eu3+ luminescence in organic solvents, while quinolin-2(1H)-one analogues selectively sensitize the Tb3+ emission. These emissions are quenched by H2O addition. Based on this behaviour, the new lanthanide antennas can be used as highly sensitive water sensors.Spanish Ministerio de Economia y Competividad SAF2012-32209 FU2015-67284-RMinisterio de Ciencia e Innovacion/Agencia Estatal de Investigacion/European Regional Development Fund CTQ2017-85658-R CTQ2015-63997-C2Consejo Superior de Investigaciones Cientificas (CSIC) 201580E07

Targeting Innate Immunity in Glioma Therapy

Currently, there is a lack of effective therapies for the majority of glioblastomas (GBMs), the most common and malignant primary brain tumor. While immunotherapies have shown promise in treating various types of cancers, they have had limited success in improving the overall survival of GBM patients. Therefore, advancing GBM treatment requires a deeper understanding of the molecular and cellular mechanisms that cause resistance to immunotherapy. Further insights into the innate immune response are crucial for developing more potent treatments for brain tumors. Our review provides a brief overview of innate immunity. In addition, we provide a discussion of current therapies aimed at boosting the innate immunity in gliomas. These approaches encompass strategies to activate Toll-like receptors, induce stress responses, enhance the innate immune response, leverage interferon type-I therapy, therapeutic antibodies, immune checkpoint antibodies, natural killer (NK) cells, and oncolytic virotherapy, and manipulate the microbiome. Both preclinical and clinical studies indicate that a better understanding of the mechanisms governing the innate immune response in GBM could enhance immunotherapy and reinforce the effects of chemotherapy and radiotherapy. Consequently, a more comprehensive understanding of the innate immune response against cancer should lead to better prognoses and increased overall survival for GBM patients

Killed in Cold Blood: An exploration of the efficacy of oncolytic adenoviruses in metastatic breast cancer

https://openworks.mdanderson.org/sumexp21/1182/thumbnail.jp